Consequences of lack of viral monitoring in predicting the effects of development of HIV drug resistance mutations during HAART in resource-limited settings (RLS) is still a matter of debate.
To ...assess, among HIV+ patients receiving their first-line HAART, prevalence of virological failure and genotypic resistance mutations pattern in a Médécins Sans Frontières/Ministry of Health programme in Busia District (Kenya).
Patients with HAART treatment for ≥12 months were eligible for the study and those with HIV-RNA ≥5000 copies/ml underwent genotypic study. Total HIV-1 RNA from Dried Blood Spots was extracted using Nuclisens method.
926 patients were included. Among 274 (29.6%) patients with detectable viral load, 55 (5.9%) experienced treatment failure (viral load >5.000 copies/ml); 61.8% were female and 10 (18.2%) had clinical failure. Median CD4 cell count was 116 cell/mm3 (IQR: 54-189). Median HIV-RNA was 32,000 copies/ml (IQR: 11000-68000). Eighteen out of 55 (33%) samples could be sequenced on PR and RT genes, with resistance associated mutations (RAMs) in 15 out of 18 samples (83%). Among patients carrying RAMs, 12/15 (81%) harboured RAMs associated to thymidine analogues (TAMs). All of them (100%) showed M184V resistance associated mutation to lamivudine as well as NNRTI's RAMS.
Virological failure rate in resource-limited settings are similar to those observed in developed countries. Resistance mutation patterns were concordant with HAART received by failing patients. Long term detectable viral load confers greater probability of developing resistance and as a consequence, making difficult to find out a cost-effective subsequent treatment regimen.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
The treatment of diethyl α,β‐dehydroaminophosphonate
1
with various arenes (ArH=toluene
2 a
, benzene
2 b
, anisole
2 c
, bromobenzene
2 d
, chlorobenzene
2 e
, benzyl alcohol
2 f
,
p
...‐xylene
2 g
) in acetic acid (AcOH) at 120 °C for 8 h in the presence of Pd(OAc)
2
(10 % mol, OAc=acetate) and AgOAc (3.4 equivalents) results in the formation of the corresponding β‐aryl derivatives
E
‐Ar(H)C=C(NHAc)P(O)(OEt)
2
3 a
–
3 g
. The reaction proceeds through double C−H activation (arene and alkene) and subsequent C−C oxidative coupling (Fujiwara–Moritani reaction), processes catalyzed by Pd and assisted by Ag. The obtained products
3 a
–
3 g
are isosteric analogs of phenylalanine and are obtained with high selectivity. Thus, geometrical
E
‐isomers have been obtained in all studied cases, however mixtures of
ortho
‐/
meta
‐/
para
‐isomers are observed when the activated position in the starting arene
2
is considered.
Oxazolones as C,N,O-tridentate ligands have been prepared in two steps from Erlenmeyer-Plöchl method followed by acid deprotection. Further reactivity with Pd(OAc)2 takes place through CH and OH ...activation to give Pd(C,N,O-oxazolone)(L) complexes, where the Pd atom is located in a rigid environment.
Display omitted
•New (Z)-4-arylidene-2-(o-hydroxyphenyl)-5(4H)-oxazolones have been prepared.•These oxazolones can be C,N,O-orthopalladated to give mononuclear complexes.•The oxazolones behave as strong C,N,O-tridentate ligands.•The incorporation of the Pd to the oxazolone takes place through CH bond activation.
The (Z)-4-aryliden-2-(2-acetoxyphenyl)-5(4H)oxazolones 1a-1c react with H2SO4 to give the corresponding (Z)-4-aryliden-2-(2-hydroxyphenyl)-5(4H)oxazolones 2a-2c.The molecular structures of 1c and 2a have been determined by X-ray diffraction methods, and show planar skeletons. Oxazolones 2a-2c are potential C,N,O-tridentate ligands towards transition metals, and their molecular design obeys to the search of a rigid environment around the metal. The reaction of Pd(OAc)2 with oxazolones 2a-2c (1:1 M ratio) in CF3CO2H or NCMe as solvents results in the synthesis of diverse complexes (3–7). As a function of the reaction conditions, two different bonding modes have been characterized: N,O-chelate in the dinuclear complexes Pd(κ2-N,O-2b,c)(μ -O2CCF3)2 (3b,c), as a result of the N-coordination and deprotonation of the hydroxy group; and C,N,O-tridentate in mononuclear complexes Pd(κ 3-C,N,O-2a,b)(L) (L = CF3CO2H 4a,b; dmso-d65a,b; NCMe 6b; pyridine 7b), obtained after N-bonding, OH deprotonation and CH bond activation. All complexes have been fully characterized by HRMS and NMR methods, showing the high stability of the C,N,O-tridentate bonding mode.
The reaction of Pd(OAc)
2
with (
Z
)-5-arylidene-4-(4
H
)-imidazolones (
2a-e
) and (
Z
)-4-arylidene-5(4
H
)-thiazolones (
3a-e
) in trifluoroacetic acid results in the corresponding orthopalladated ...dinuclear complexes (
4a-e
, imidazolones;
11a-d
, thiazolones) with trifluoroacetate bridges through regioselective C-H activation at the
ortho
position of the 4-arylidene group. Compound
4e
, which contains an imidazolone substituted at 2- and 4-positions of the arylidene ring with methoxide groups and exhibits strong push-pull charge transfer, is an excellent precursor for the synthesis of fluorescent complexes with green yellowish emission and remarkable quantum yields. Breaking the bridging system with pyridine yields the mononuclear complex
5e
(
Φ
F
= 5%), while metathesis of trifluoroacetate ligands with chloride leads to the dinuclear complex
6e
, also a precursor of fluorescent complexes by breaking the chloride bridging system with pyridine (
7e
,
Φ
F
= 7%), or by substitution of chloride ligands with pyridine (
8e
,
Φ
F
= 15%) or acetylacetonate (
9e
,
Φ
F
= 2%). In addition to notable photophysical properties, dinuclear complexes
4
and
11
also exhibit significant photochemical reactivity. Thus, irradiation of orthopalladates
4a-c
and
11a-c
in CH
2
Cl
2
with blue light (465 nm) proceeds
via
2 + 2 photocycloaddition of the C&z.dbd;C double bonds of imidazolone and thiazolone ligands, yielding the corresponding cyclobutane-bridging diaminotruxillic derivatives
10a-c
and
12a-c
, respectively.
The incorporation of Pd into the molecular framework of 4-arylidene-imidazolones or thiazolones generates platforms with remarkable photophysical and photochemical properties. Quantum yields of up to 15% and a clear photoreactivity have been achieved.
Weakly fluorescent (Z)-4-arylidene-5-(4H)-oxazolones (1), ΦPL < 0.1%, containing a variety of conjugated aromatic fragments and/or charged arylidene moieties, have been orthopalladated by reaction ...with Pd(OAc)2. The resulting dinuclear complexes (2) have the oxazolone ligands bonded as a C^N-chelate, restricting intramolecular motions involving the oxazolone. From 2, a variety of mononuclear derivatives, such as Pd(C^N-oxazolone)(O2CCF3)(py) (3), Pd(C^N-oxazolone)(py)2(ClO4) (4), Pd(C^N-oxazolone)(Cl)(py) (5), and Pd(C^N-oxazolone)(X)(NHC) (6, 7), have been prepared and fully characterized. Most of complexes 3–6 are strongly fluorescent in solution in the range of wavelengths from green to yellow, with values of ΦPL up to 28% (4h), which are among the highest values of quantum yield ever reported for organometallic Pd complexes with bidentate ligands. This means that the introduction of the Pd in the oxazolone scaffold produces in some cases an amplification of the fluorescence of several orders of magnitude from the free ligand 1 to complexes 3–6. Systematic variations of the substituents of the oxazolones and the ancillary ligands show that the wavelength of emission is tuned by the nature of the oxazolone, while the quantum yield is deeply influenced by the change of ligands. TD-DFT studies of complexes 3–6 show a direct correlation between the participation of the Pd orbitals in the HOMO and the loss of emission through non-radiative pathways. This model allows the understanding of the amplification of the fluorescence and the future rational design of new organopalladium systems with improved properties.
Determinants of late diagnosis of HIV infection in Spain Apodaca, María José Fuster-Ruiz de; Molero, Fernando; Nouvilas, Encarnación ...
Intervención psicosocial/Intervención psicosocial,
09/2014, Letnik:
23, Številka:
3
Journal Article
Recenzirano
Odprti dostop
The main goal of this study was to analyse the determinants of late diagnosis of HIV infection. Secondly, we studied the role of the perception of risk and sexual orientation in HIV testing. ...Twenty-five people with late HIV diagnosis were interviewed. They were contacted through hospitals and non-governmental organizations (NGOs). To design the interview, we integrated the variables considered in the main models of health-related behaviour. We followed a mixed strategy of analysis. Firstly, we carried out thematic analysis of the interviews, followed by quantitative analysis of the initially qualitative data. The results revealed that the most relevant determinants were the appraisal of the threat of HIV and the low perception of HIV risk. Also, the study found many missed opportunities for diagnosis in health-care setting. Low perception of HIV risk was related to unrealistic optimism, low levels of information about HIV, and the presence of stereotypes about people with HIV. High perception of HIV risk was related to strategies to avoid testing. Homosexuals reported a more positive balance between the benefits of knowing their diagnosis and having the disease. The results provide clues that can guide the design of future strategies to promote early diagnosis.
El objetivo principal de este estudio fue analizar los determinantes del diagnóstico tardío de la infección por VIH. Asimismo, se estudió el papel que jugaban en ello la percepción de riesgo y la orientación sexual. Se entrevistó a 25 personas con VIH, con las que se estableció contacto a través de hospitales y de organizaciones no gubernamentales (ONG). Para el diseño del guión de la entrevista se partió de una integración de las variables consideradas en los principales modelos de conductas de salud. Se siguió una estrategia mixta de análisis. Primeramente, se realizó análisis temático de las entrevistas. Seguidamente, se realizaron análisis cuantitativos sobre los datos cualitativos. Se halló que los determinantes más relevantes eran la valoración de amenaza del VIH y la baja percepción de riesgo. Se hallaron también oportunidades perdidas de diagnóstico en el sistema sanitario. La baja percepción de riesgo se asociaba con el optimismo irrealista, la poca información sobre el VIH y los estereotipos sobre las personas con VIH. La alta percepción de riesgo se relacionaba con las estrategias de evitación del test. Los discursos de las personas homosexuales mostraron un balance más positivo de los beneficios de conocer el diagnóstico. Los resultados sugieren claves que pueden guiar el diseño de futuras estrategias de promoción del diagnóstico precoz.
Synthesis of Bis-oxazolones Sierra, Sonia; Dalmau, David; Alegre-Requena, Juan V ...
International journal of molecular sciences,
04/2023, Letnik:
24, Številka:
8
Journal Article
Recenzirano
The irradiation of 2-aryl-4-(E-3′-aryl-allylidene)-5(4H)-oxazolones 1 with blue light (456 nm) in the presence of Ru(bpy)sub.3(BFsub.4)sub.2 (bpy = 2,2′-bipyridine, 5% mol) gives the unstable ...cyclobutane-bis(oxazolones) 2 by 2+2-photocycloaddition of two oxazolones 1. Each oxazolone contributes to the formation of 2 with a different C=C bond, one of them reacting through the exocyclic C=C bond, while the other does so through the styryl group. Treatment of unstable cyclobutanes 2 with NaOMe/MeOH produces the oxazolone ring opening reaction, affording stable styryl-cyclobutane bis(amino acids) 3. The reaction starts with formation of the Tsub.1 excited state of the photosensitizer sup.3Ru*(bpy)sub.3sup.2+, which reacts with Ssub.0 of oxazolones 1 through energy transfer to give the oxazolone Tsub.1 state sup.3(oxa*)-1, which is the reactive species and was characterized by transient absorption spectroscopy. Measurement of the half-life of sup.3(oxa*)-1 for 1a, 1b and 1d shows large values for 1a and 1b (10-12 μs), while that of 1d is shorter (726 ns). Density functional theory (DFT) modeling displays strong structural differences in the Tsub.1 states of the three oxazolones. Moreover, study of the spin density of Tsub.1 state sup.3(oxa*)-1 provides clues to understanding the different reactivity of 4-allylidene-oxazolones described here with respect to the previously reported 4-arylidene-oxazolones.
The irradiation of (Z)-2-phenyl-4-aryliden-5(4H)-thiazolones 2 with blue light (465 nm) in CH2Cl2 solution promotes 2 + 2-photocycloaddition of the exocyclic C═C bonds and the formation of the ...dispirocyclobutanes 3. This reaction takes place with high stereoselectivity, given that the ε-isomer (1,3 head-to-tail syn coupling) is formed in more than 90% yield in most of the cases. However, irradiation of 5(4H)-thiazolones 2 with blue light (456 nm) in dry MeOH in the presence of BF3·OEt2 leads to the monospirocyclobutanes 4 with full stereoselectivity, also affording the ε-isomer. A ring-opening reaction of only one of the thiazolone rings appears to have taken place in 4 upon methanolysis, leading to the corresponding ester and thioamide groups. The treatment of free 4-aryliden-5(4H)-thiazolones 2 with a base in alcohol (NaOR/ROH) also produces a ring-opening reaction of the heterocycle by methanolysis, although, under these reaction conditions, further intramolecular S-attack at the exocyclic C(H)═C bond and cyclization is observed, forming the dihydrothiazoles 5 or 6 as mixtures of cis (RS/SR)- and trans (RR/SS)-isomers with high diastereomeric excess. trans-(RR/SS)-Dihydrothiazoles 6 can be isolated as pure diastereoisomers by column chromatography. Surprisingly, dihydrothiazoles 5 can also be obtained by the treatment of 4-aryliden-5(4H)-thiazolones 2 with BF3·OEt2 in methanol in the absence of a base.The irradiation of (Z)-2-phenyl-4-aryliden-5(4H)-thiazolones 2 with blue light (465 nm) in CH2Cl2 solution promotes 2 + 2-photocycloaddition of the exocyclic C═C bonds and the formation of the dispirocyclobutanes 3. This reaction takes place with high stereoselectivity, given that the ε-isomer (1,3 head-to-tail syn coupling) is formed in more than 90% yield in most of the cases. However, irradiation of 5(4H)-thiazolones 2 with blue light (456 nm) in dry MeOH in the presence of BF3·OEt2 leads to the monospirocyclobutanes 4 with full stereoselectivity, also affording the ε-isomer. A ring-opening reaction of only one of the thiazolone rings appears to have taken place in 4 upon methanolysis, leading to the corresponding ester and thioamide groups. The treatment of free 4-aryliden-5(4H)-thiazolones 2 with a base in alcohol (NaOR/ROH) also produces a ring-opening reaction of the heterocycle by methanolysis, although, under these reaction conditions, further intramolecular S-attack at the exocyclic C(H)═C bond and cyclization is observed, forming the dihydrothiazoles 5 or 6 as mixtures of cis (RS/SR)- and trans (RR/SS)-isomers with high diastereomeric excess. trans-(RR/SS)-Dihydrothiazoles 6 can be isolated as pure diastereoisomers by column chromatography. Surprisingly, dihydrothiazoles 5 can also be obtained by the treatment of 4-aryliden-5(4H)-thiazolones 2 with BF3·OEt2 in methanol in the absence of a base.
The irradiation of (Z)-2-phenyl-4-aryliden-5(4H)-thiazolones 2 with blue light (465 nm) in CH2Cl2 solution promotes 2 + 2-photocycloaddition of the exocyclic CC bonds and the formation of the ...dispirocyclobutanes 3. This reaction takes place with high stereoselectivity, given that the ε-isomer (1,3 head-to-tail syn coupling) is formed in more than 90% yield in most of the cases. However, irradiation of 5(4H)-thiazolones 2 with blue light (456 nm) in dry MeOH in the presence of BF3·OEt2 leads to the monospirocyclobutanes 4 with full stereoselectivity, also affording the ε-isomer. A ring-opening reaction of only one of the thiazolone rings appears to have taken place in 4 upon methanolysis, leading to the corresponding ester and thioamide groups. The treatment of free 4-aryliden-5(4H)-thiazolones 2 with a base in alcohol (NaOR/ROH) also produces a ring-opening reaction of the heterocycle by methanolysis, although, under these reaction conditions, further intramolecular S-attack at the exocyclic C(H)C bond and cyclization is observed, forming the dihydrothiazoles 5 or 6 as mixtures of cis (RS/SR)- and trans (RR/SS)-isomers with high diastereomeric excess. trans-(RR/SS)-Dihydrothiazoles 6 can be isolated as pure diastereoisomers by column chromatography. Surprisingly, dihydrothiazoles 5 can also be obtained by the treatment of 4-aryliden-5(4H)-thiazolones 2 with BF3·OEt2 in methanol in the absence of a base.
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